Biology subjects

Beis, D.

Publications and source records attributed to Beis, D..

3 recordsLinked to original sources

bioRxiv2022

Cfdp1 is Essential for Cardiac Development and Function

Cardiovascular diseases (CVDs) are the prevalent cause of mortality worldwide and account for the most common noncommunicable disease. CVDs describe a wide spectrum of disorders affecting the proper function, physiology and morphogenesis of the heart and blood vessels. The risk of developing cardiovascular diseases is modulated by a combination of environmental and genetic effectors. Thus, its highly important to identify candidate genes and elucidate their role in the manifestation of the disease. Large-scale human studies have revealed the implication of Craniofacial Development Protein 1 (CFDP1) in coronary artery disease (CAD). CFDP1 belongs to the evolutionary conserved Bucentaur (BCNT) family and up to date, its function and mechanism of action in Cardiovascular Development is still unclear. In this study, we utilize zebrafish to investigate the role of cfdp1 in the developing heart due to the high genomic homology, similarity in heart physiology and the ease of experimentally manipulation. We showed that cfdp1 is expressed during development and at 120 hours post fertilization its expression is restricted to the region of the heart and the head. We then generated a cfdp1-null zebrafish line using CRISPR-Cas9 system which led to a lethal phenotype since knockout embryos do not reach adulthood. cfdp1-/- embryos develop arrhythmic hearts and defective cardiac performance exhibiting statistically significant differences in heart features including End Diastolic Volume, Cardiac Output, Ejection Fraction and Stroke Volume. Myocardial trabeculation is also impaired in cfdp1-/- embryonic hearts, implying its regulatory role also in this developmental process. Findings from both knockdown and knockout experiments showed that abrogation of cfdp1 leads to downregulation of Wnt signaling in embryonic hearts during valve development but without affecting Notch activation in this process.

developmental biology↗

bioRxiv2022

Return of the Tbx5; lineage-tracing reveals ventricular cardiomyocyte-like precursors in the injured adult mammalian heart

The single curative measure for heart failure patients is total heart transplantation, which is limited due to a shortage of donors, the need for immunosuppression and economic costs. Therefore, there is an urgent unmet need for identifying cell populations capable of cardiac regeneration that we will be able to trace and monitor. Injury to the adult mammalian cardiac muscle, often leads to a heart attack through the irreversible loss of a large number of cardiomyocytes, due to an idle regenerative capability. Recent reports in zebrafish indicate that Tbx5a is a vital transcription factor for cardiomyocyte regeneration. Preclinical data underscore the cardioprotective role of Tbx5 upon heart failure. Data from our earlier murine developmental studies have pinpointed a prominent unipotent Tbx5-expressing embryonic cardiac precursor cell population able to form cardiomyocytes, in vivo, in vitro and ex vivo. Using a developmental approach to an adult heart injury model and by employing a lineage-tracing mouse model as well as the use of single-cell RNA-seq technology, we identify a Tbx5-expressing ventricular cardiomyocyte-like precursor population, in the injured adult mammalian heart. The transcriptional profile of that precursor cell population is closer to that of neonatal than embryonic cardiomyocyte precursors. Tbx5, a cardinal cardiac development transcription factor, lies in the centre of a ventricular adult precursor cell population, which seems to be affected by neurohormonal spatiotemporal cues. The identification of a Tbx5-specific cardiomyocyte precursor-like cell population, which is capable of dedifferentiating and potentially deploying a cardiomyocyte regenerative program, provides a clear target cell population for translationally-relevant heart interventional studies.

cell biology↗

bioRxiv2019

Cardiac valve regeneration in adult zebrafish: importance of TGF-β signaling in new tissue formation

Cardiac valve disease can lead to severe cardiac dysfunction and is thus a frequent cause of morbidity and mortality. Its main treatment is valve replacement, which is currently greatly limited by the poor recellularization and tissue formation potential of the implanted valves. As we still lack suitable animal models to identify modulators of these processes, here we used the adult zebrafish and found that, upon valve decellularization, they initiate a striking regenerative program that leads to the formation of new functional valves. After injury, endothelial and kidney marrow-derived cells undergo cell cycle re-entry and differentiate into new extracellular matrix-secreting valve cells. The Transforming Growth Factor beta (TGF{beta}) signaling pathway promotes this process by enhancing progenitor cell proliferation as well as valve cell differentiation. These findings reveal a key role for TGF{beta} signaling in valve regeneration and also establish the zebrafish as a model to identify and test factors promoting valve recellularization and growth.

developmental biology↗